Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study

OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse events (AEs) and the incidence and reasons for withdrawals. Visits were scheduled at 3, 6, 9, and 12 mo, and investigators were instructed to report all AEs. At 6 and 12 mo, vital signs were recorded and a physical examination was performed. RESULTS: A total of 318 patients were enrolled (double-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection (7%), nasopharyngitis (5%), headache (5%), and abdominal pain (4%); 111 (35%) patients withdrew. The most common reasons for withdrawal were lack of efficacy (12%), symptom improvement (8%), and withdrawn consent (6%). Ten patients (3%) withdrew because of AEs. CONCLUSION: Long-term treatment with tolterodine ER was well tolerated in children with UUI.     

Riolan's arch: confusing, misnomer, and obsolete. A literature survey of the connection(s) between the superior and inferior mesenteric arteries

BACKGROUND: There are 2 interpretations of Riolan's arch: (1) Riolan's arch is identical to a central part of the marginal artery (MA), connecting the superior (SMA) and the inferior mesenteric (IMA) arteries; and (2) Riolan's arch represents a rare artery, connecting the SMA and the IMA. The current review aims to emphasize the clinical importance of the colon's vasculature and to show the feasibility of abolishing the terms "Riolan's arch" and "meandering mesenteric artery." METHODS: A literature survey was performed. RESULTS: It appears that no distinct identity can be ascribed to Riolan's arch and that the "meandering mesenteric artery" represents an angiographically hypertrophied MA and/or the ascending branch of the left colic artery. However, a rare, centrally located, communicating artery has been described. Generally, the MA is sufficient for left colic circulation after ligation of the IMA, but at the splenic flexure, patency of the ascending branch of the left colic artery can be primordial. CONCLUSION: As connections between the SMA and the IMA can be adequately described using structures mentioned in Terminologica Anatomica, the terms "Riolan's arch" and "meandering mesenteric artery" should be abolished.     

Normal reference ranges for semen quality and their relations to fecundity

Several recent studies have shown that the fecundity of a man decreases progressively with sperm concentrations below 40 million spermatozoa per mL. Therefore, it is unfortunate that the new World Health Organization guidelines for semen analysis recommend lowering the lower cutoff value for normal sperm concentration from 20 to 15 million spermatozoa per mL. As a result large groups of subfertile men across the world may not receive appropriate andrological help in the future.     

The final follow-up plain radiograph is sufficient for clinical evaluation of polyethylene wear in total hip arthroplasty: A study of validity and reliability

Background and purpose

Radiostereometric analysis (RSA) is a highly accurate tool for assessment of polyethylene (PE) wear in total hip arthroplasty (THA); however, PE wear measurements in clinical studies are often limited to plain radiographs. We evaluated the agreement between PE wear measured with PolyWare software, which uses plain radiographs, and by model-based RSA, which uses stereo radiographs.

Methods

Measurements of PE wear postoperatively and at final follow-up (after mean 6 years) on plain radiographs of 12 patients after cementless THA were evaluated with PolyWare software and the results were compared with those from RSA as the gold standard (Model-based RSA using elementary geometrical shape models; EGS-RSA). With PolyWare, we either used the final radiographic follow-up (PW1) only or both the postoperative follow-up and the final follow-up (PW2).

Results

The 2D mean wear measured (in mm) was 0.80, 1.07, and 0.60 for the PW2, PW1, and RSA method. 2D intra-method repeatability was similar for PW1 and RSA with limits of agreement (LOAs, in mm) of ± 0.22, and ± 0.23, respectively. 2D inter-method concurrent validity was best between PW1 and EGS-RSA with LOAs of ± 0.55. For 2D linear wear measurements, the PW1 method had a clinical repeatability similar to that of RSA.

Interpretation

PW1 is sufficient for retrospective determination of 2D wear from medium-term wear measurements above 0.5 mm, It alleviates the need for baseline plain radiographs, has a clinical precision similar to that of RSA, and is easy and inexpensive to use.Wear of polyethylene (PE) components is widely regarded as the main factor limiting longevity of total hip arthroplasty (THA) (Cooper et al. 1992). Clinical studies have shown that periprosthetic osteolysis and aseptic loosening is strongly related to wear rates of above 0.2 mm/year (Sochart 1999, Dowd et al. 2000).Radiostereometric analysis (RSA) is the most accurate tool for in vivo assessment of PE wear (Kärrholm et al. 1997, von Schewelov et al. 2004, Bragdon et al. 2006), and it is regarded as the gold standard (Ilchmann et al. 1995). However, many radiographic in vivo studies of PE wear in THA are restricted to measurements on plain radiographs because the RSA set-up is expensive and not widely available. Measurement of PE wear on plain radiographs is often limited to 2D analysis because poor quality of cross-table lateral radiographs is a common problem (Sychterz et al. 1999b, 2001). Although PE wear is known to occur multidirectionally (Yamaguchi et al. 1997, Akisue et al. 1999), the bulk of the wear is detectable on the anterior-posterior radiographs alone (Sychterz et al. 1997, Hui et al. 2003, Martell et al. 2003). Based on the availability of radiographs and investigator preferences, some authors favor analysis of serial radiographs (Sychterz et al. 1997, Kim et al. 2001, Hernigou and Bahrami 2003) to describe the pattern of wear and the steady-state wear (Sychterz et al. 1999a, Bragdon et al. 2006), whereas others use 2 radiographic follow-ups (postoperative and latest) (Kraay et al. 2006), or only the latest radiographic follow-up with the assumption of zero wear at baseline (Norton et al. 2002)Little is known about the conformity between PE wear results measured with RSA and computerized methods using plain radiographs (Ilchmann et al. 1995, von Schewelov et al. 2004, Bragdon et al. 2006). Our group has questioned the conformity of 2D PE wear measurements based on serial, 2, or 1 radiographic follow-up (Stilling et al. 2009b). We determined that there was a statistically significant difference between all approaches, but we were unable to determine which strategy best reflected the true extent of wear (Stilling et al. 2009b). In addition, we recently showed that model-based RSA is an accurate tool for measurement of PE wear in good agreement with the true wear (Stilling 2009).We have now studied the intra-method repeatability and concurrent validity between 2 methods (PolyWare and EGS-RSA) for measurement of PE wear in THA, in a group of patients with an average follow-up of 6 years. We wanted to determine (1) whether there would be a difference in repeatability between the methods, (2) whether there would be a difference in wear measured using 1 or 2 radiographic follow-ups with the PolyWare method, and (3) whether either of the 2 PolyWare measurement strategies (1 or 2 radiographic follow-ups) would give results similar to the wear measured by RSA (concurrent validity).     

A randomized, controlled trial comparing local infiltration analgesia with epidural infusion for total knee arthroplasty

Background

There have been few studies describing wound infiltration with additional intraarticular administration of multimodal analgesia for total knee arthroplasty (TKA). In this study, we assessed the efficacy of wound infiltration combined with intraarticular regional analgesia with epidural infusion on analgesic requirements and postoperative pain after TKA.

Methods

40 consecutive patients undergoing elective, primary TKA were randomized into 2 groups to receive either (1) intraoperative wound infiltration with 150 mL ropivacaine (2 mg/mL), 1 mL ketorolac (30 mg/mL), and 0.5 mL epinephrine (1 mg/mL) (total volume 152 mL) combined with intraarticular infusion (4 mL/h) of 190 mL ropivacaine (2 mg/mL) plus 2 mL ketorolac (30 mg/mL) (group A), or (2) epidural infusion (4 mL/h) of 192 mL ropivacaine (2 mg/mL) combined with 6 intravenous administrations of 0.5 mL ketorolac (30 mg/mL) for 48 h postoperatively (group E). For rescue analgesia, intravenous patient-controlled-analgesia (PCA) morphine was used.Morphine consumption, intensity of knee pain (0–100 mm visual analog scale), and side effects were recorded. Length of stay and corrected length of stay were also recorded (the day-patients fulfilled discharge criteria).

Results

The median cumulated morphine consumption, pain scores at rest, and pain scores during mobilization were reduced in group A compared to group E. Corrected length of stay was reduced by 25% in group A compared to group E.

Interpretation

Peri- and intraarticular analgesia with multimodal drugs provided superior pain relief and reduced morphine consumption compared with continuous epidural infusion with ropivacaine combined with intravenous ketorolac after TKA.Total knee arthroplasty (TKA) usually results in severe postoperative pain. Continuous epidural infusion with a local anesthetic is a standard regime for postoperative analgesia after TKA. Epidural analgesia and also peripheral nerve block analgesia have been shown to reduce opioid consumption compared with intravenous patient-controlled analgesia (PCA). Even though both modalities reduce the occurrence of the well-known side effects of opioid drugs, they involve extra equipment and are associated with substantial side effects (Choi et al. 2003, Davies et al. 2004, Boezaart 2006). Wound infiltration with multimodal analgesia has been a controversial issue for many years (Dahl et al. 1994). Different modes of perioperative analgesia either without or combined with intraarticular infusion or bolus injection(s) for both TKA and total hip arthroplasty have been described (Bianconi et al. 2003, Rasmussen et al. 2004, Reilly et al. 2005, Andersen et al. 2007a, b). Only a few studies have described high-volume peri- and intraarticular analgesia for TKA (Busch et al. 2006, Vendittoli et al. 2006, Toftdahl et al. 2007). The hypothesis in our trial was that wound infiltration and intraarticular infusion of ropivacaine and ketorolac would reduce opioid consumption during the active treatment period (0–48 h postoperatively) after TKA compared to epidural infusion of ropivacaine and intravenous ketorolac. Primary outcome was 48-h opioid use. Secondary outcomes included pain at rest and during mobilization, side effects, length of hospital stay (LOS), and corrected length of stay (the day-patients fulfilled discharge criteria).     

Effect of graded hyperventilation on cerebral metabolism in a cisterna magna blood injection model of subarachnoid hemorrhage in rats

In subarachnoid hemorrhage (SAH) with cerebrovascular instability, hyperventilation may induce a risk of inducing or aggravating cerebral ischemia. We measured cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRglc), and lactate (CMRlac) at different PaCO2 levels after experimental SAH in rats (injection of 0.07 mL of autologous blood into the cisterna magna). Four groups of Sprague-Dawley male rats were studied at predetermined PaCO2 levels: group A: normocapnia (5.01-5.66 kPa [38.0-42.0 mm Hg]); group B: slight hyperventilation (4.34-5.00 kPa [32.5-37.5 mm Hg]); group C: moderate hyperventilation (3.67-4.33 kPa [27.5-32.4 mm Hg]); group D: profound hyperventilation (3.00-3.66 kPa [22.5-27.4 mm Hg]). Each of the four groups included eight rats with SAH and eight sham-operated controls. CBF was determined by the intracarotid Xe method; CMRo2, CMRglc, and CMRlac were obtained by cerebral arteriovenous differences. In both SAH rats and controls, hyperventilation decreased CBF in proportion to the decrement in PaCO2 without affecting either CMRO2, CMRglc, or CMRlac. In groups C and D, CBF decreased by 20%-35%, but CMRs were maintained by a compensatory increase in oxygen extraction fraction (OEF). The results show that even profound hyperventilation in this model of SAH is associated with an adequate increase in OEF so that CMRs of oxygen, glucose, and lactate remain similar to levels observed in normocapnic conditions.     

Why are patients still in hospital after fast-track,unilateral unicompartmental knee arthroplasty

Background and purpose — Previous studies have investigated risk factors related to prolonged length of stay following total knee arthroplasty (TKA), but little is known about specific factors resulting in continued hospitalization within the 1st postoperative days after unicompartmental knee arthroplasty (UKA). We investigated what specific factors prevent patients from being discharged on the day of surgery (DOS) and the first postoperative day (POD-1) following primary UKA in a fast-track setting.Patients and methods — We prospectively collected data on 100 consecutive and unselected medial UKA patients operated from December 2017 to May 2019. All patients were operated in a standardized fast-track setup with functional discharge criteria continuously evaluated from DOS and until discharge.Results — Median length of stay for the entire cohort was 1 day. 22% and 78% of all patients were discharged on DOS and POD-1, respectively. Lack of mobilization and pain separately delayed discharge in respectively 78% and 24% of patients on DOS. The main reasons for lack of mobilization were motor blockade (37%) and logistical factors (26%). For patients placed 1st or 2nd on the operating list, we estimate that the same-day discharge rate would increase to 55% and 40% respectively, assuming that pain and mobilization were successfully managed.Interpretation — One-fifth of unselected UKA patients operated in a standardized fast-track setup were discharged on DOS. Pain and lack of mobilization were the major reasons for continued hospitalization within the initial postoperative 24–48 hours. Strategies aimed at decreasing length of stay after UKA should strive to improve analgesia and postoperative mobilization.

The number of unicompartmental knee arthroplasties (UKAs) performed in patients suffering from osteoarthritis has steadily increased. UKA has the potential benefit of not only improving patient-reported outcomes, but also to reduce morbidity, complications, and cost (Liddle et al. 2014, Beard et al. 2019). In the United Kingdom, 9% of all primary knee arthroplasties performed in 2018 were UKAs while this number is as high as 20% in Denmark (Danish Knee Arthroplasty Register 2019, National Joint Registry for England 2019).UKA is effective and safe when performed in a fast-track setting and outpatient UKA in selected patients has been shown to be feasible and safe (Munk et al. 2012, Cross and Berger 2014, Bovonratwet et al. 2017, Kort et al. 2017). However, the number of patients actually being discharged on DOS that were scheduled for outpatient surgery differs between studies and ranges from 37% to 100% (Gondusky et al. 2014, Bradley et al. 2017, Jenkins et al. 2019, Rytter et al. 2019).Studies have shown an association between increased length of stay (LOS) and an increase in both complication and readmission rates (Otero et al. 2016). In order to reduce LOS and increase patient satisfaction, a focus on successfully managing well-defined discharge criteria in a multimodal approach is imperative (Husted et al. 2008, Cross and Berger 2014). In addition, decreased LOS and outpatient procedures are associated with financial benefits, which have further fueled interest in decreasing LOS and ensuring DOS discharged following UKA (Bradley et al. 2017). Finally, decreased LOS is also shown to increase patient satisfaction levels (Reilly et al. 2005, Richter and Diduch 2017).A study has been conducted to explore reasons for prolonged hospitalization in a fast-track setting following TKA (Husted et al. 2011). However, in spite of a growing number of UKAs performed each year, no study explicitly exploring reasons for prolonged hospitalization beyond DOS following UKA in a fast-track setting has been published at present.Therefore, we investigated reasons for continued hospitalization beyond DOS following UKA in a fast-track setting.     

Assessment of automated screening for treatment-requiring diabetic retinopathy

PURPOSE: To evaluate fundus photographic image analysis combining automated detection of red lesions, bright lesions, and image quality as a means of identifying treatment-requiring diabetic retinopathy in a screening population of diabetic patients. METHODS: This was a retrospective cross-sectional study of 106 patients from a diabetic retinopathy screening clinic referred for photocoagulation treatment in the period from January 1996 to May 2002 on the basis of mydriatic 60-degree 35-mm color transparency fundus photography. One fovea-centered fundus photograph and one centered nasal of the optic disk from each of a subject's two eyes was selected for digitization and analyzed using a previously tested computerized red-lesion detection algorithm in combination with a new algorithm for detection of bright lesions and image quality. The algorithm was calibrated on an independent set of fundus photographs. RESULTS: Automated red-lesion detection identified 104 of 106 patients requiring photocoagulation treatment, whereas bright-lesion detection identified only 91 of the 106 patients. Two patients who were not identified by either lesion detection algorithm were automatically detected as having poor image quality in one or both eyes. In the study sample, the risk of missing treatment-requiring retinopathy patients from being detected was 0.0% (estimated CI(95) 0.0-3.4%). CONCLUSIONS: The combination of automated detection of red lesions and poor image quality identified all treatment-requiring diabetic retinopathy patients in the study sample. No additional information was contributed by the automated bright-lesion detection.